Higher density of ECM composition in pancreatic cancer correlates with reduced drug delivery

Abstract

Pancreatic ductal adenocarcinomas (PDACs) are often treatment resistant, and as such widefield imaging methods for the evaluation of ECM composition are needed. Here we present a method to measure the relative abundance of ECM diffracting components in PDAC samples alongside drug penetration in widefield images. Orthotopic mouse PDAC xenografts are grown and assessment of drug penetration as well as ECM composition is done using co-registration of scanning x-ray diffraction (XRD) and EGFR-specific drug penetration fluorescent widefield images. Preliminary data suggests a strongly negative correlation between abundance of diffracting ECM components and penetration of large drugs in solid tumors. This methodology may be used to provide crucial insights into both drug-development approaches and multi-therapeutic treatment strategies in late stage PDAC patients presenting with ECM desmoplasia.